During the development of a biotherapeutic-producing microorganism, the success of a potential product depends on mimicking industrial-scale conditions. Current approaches, however, often create very different conditions in small and large batches. Volkert van Steijn, PhD, associate professor of chemical engineering at the Delft University of Technology in the Netherlands, and his colleagues reviewedthe potential of microbioreactors as a solution to that problem
Nonetheless, screening the mutants quickly usually relies on technology that lacks the nutrient control used at industrial scale. For example, scientists typically screen the mutants in microtiter plates under batch conditions, in which no additional nutrients are added during an experiment. The low volume of a microtiter plate’s wells—say, 10–2,000 µL—caters to high-throughput analysis but hinders the options for controlling the conditions.
But that combination might come from microbioreactors, which can be created with microtiter plates, microfluidic chambers, or microfluidic droplet-based approaches. To make a microbioreactor from microtiter plates, for instance, it’s modified to provide fed-batch control of nutrients, which is commonly used in the industrial process. Nonetheless, Steijn and his colleagues pointed out the ongoing difficulty of controlling such a small environment and the challenges in making the modified microtiter plates. Consequently, the modified plates usually include a small number of wells, just 24 in some cases, and that limits the throughput of the screening.
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